Cancer develops in a hierarchical pattern originating from cancer stem cells (CSCs) that self-renew and give rise to more differentiated cancer cells that are unable to initiate the disease. Cancer stem cells have been identified in several types of cancer, including acute myeloid leukemia (AML), breast cancer, head and neck cancer, glioma, lung cancer, prostate cancer, mesenchymal neoplasm, melanoma, and colon cancer to name a few. Methods of selecting CSCs include using a combination of cell surface markers such as, EpCAM, CD166, CD144, CD133, and CD44.
Cancer stem cells are key to the progression of cancer, and are resistant to chemotherapeutic drugs. CSCs remain quiescent until they become genetically unstable and clonally expand during a pre-cancer disease phase. Afterwards, the CSCs develop or differentiate into different cancer cell types such as progenitor cancer cells, precursor cancer cells, and finally, terminally differentiated cancer cells.
Leukemia stem cells (LSCs) have been characterized in chronic myeloid leukemia (CML) and in some forms of AML (Schurch et al., Front Immunolo, 2013, 4:496). To date, stem cells from acute lymphoblastic leukemia (ALL) have not been identified. LSCs are resistant to most current treatments such as radiotherapy and chemotherapy. Thus, LSCs are considered the main cause of drug resistance and disease relapse.
Challenges remain for isolating CSCs including LSCs because CSCs are phenotypically heterogeneous and are relatively unstable. There remains a need in the art for methods of isolating CSCs from an individual or from cell culture, such that these cells can be, for example, studied further or used to develop targeted therapies for cancer. The present invention provides novel methods that satisfy this need and are advantageous over the current methods for isolating CSC, including LSCs.